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      The role of MiRNA-21 in gliomas: Hope for a novel therapeutic intervention?

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          Graphical abstract

          Highlights

          • MIRNA-21 is consistently upregulated in gliomas.

          • It suppresses apoptosis and promotes tumor invasion.

          • It is involved in resistance against chemo- and radiotherapy.

          • Research should focus on inhibiting MiRNA-21 in human brains.

          Abstract

          Gliomas are the most common primary brain tumors in adults. They are generally very resistant to treatment and are therefore associated with negative outcomes. MicroRNAs (miRNAs) are small, non-coding RNA molecules that affect many cellular processes by regulating gene expression and, post-transcriptionally, the translation of mRNAs. MiRNA-21 has been consistently shown to be upregulated in glioma and research has shown that it is involved in a wide variety of biological pathways, promoting tumor cell survival and invasiveness. Furthermore, it has been implicated in resistance to treatment, both against chemotherapy and radiotherapy. In this review, we gathered the existent data on miRNA-21 and gliomas, in terms of its expression levels, association with grade and prognosis, the pathways it involves and its targets in glioma, and finally how it leads to treatment resistance. Furthermore, we discuss how this knowledge could be applied in clinical practice in the years to come. To our knowledge, this is the first review to assess in extent and depth the role of miRNA-21 in gliomas.

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          Most cited references174

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          Shedding light on the cell biology of extracellular vesicles

          Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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            The 2007 WHO Classification of Tumours of the Central Nervous System

            The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.
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              MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.

              MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by targeting the mRNA of protein-coding genes for either cleavage or repression of translation. The roles of miRNAs in lineage determination and proliferation as well as the location of several miRNA genes at sites of translocation breakpoints or deletions has led to the speculation that miRNAs could be important factors in the development or maintenance of the neoplastic state. Here we show that the highly malignant human brain tumor, glioblastoma, strongly over-expresses a specific miRNA, miR-21. Our studies show markedly elevated miR-21 levels in human glioblastoma tumor tissues, early-passage glioblastoma cultures, and in six established glioblastoma cell lines (A172, U87, U373, LN229, LN428, and LN308) compared with nonneoplastic fetal and adult brain tissues and compared with cultured nonneoplastic glial cells. Knockdown of miR-21 in cultured glioblastoma cells triggers activation of caspases and leads to increased apoptotic cell death. Our data suggest that aberrantly expressed miR-21 may contribute to the malignant phenotype by blocking expression of critical apoptosis-related genes.
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                Author and article information

                Contributors
                Journal
                Toxicol Rep
                Toxicol Rep
                Toxicology Reports
                Elsevier
                2214-7500
                06 November 2020
                2020
                06 November 2020
                : 7
                : 1514-1530
                Affiliations
                [a ]Department of Neurology, Laboratory of Neurogenetics, University of Thessaly, University Hospital of Larissa, Larissa, Greece
                [b ]Public Health Laboratories, Hellenic Pasteur Institute, Athens, Greece
                [c ]Department of Cardiothoracic Surgery, University General Hospital of Heraklion, Medical School, University of Crete, 71003 Heraklion, Greece
                [d ]Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece
                [e ]Department of Neurology, School of Medicine, University of Crete, 71003 Heraklion, Greece
                [f ]Department of Rheumatology and Clinical Immunology, University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis 40500, Larissa, Greece
                [g ]Department of Neurosurgery, University of Thessaly, University Hospital of Larissa, Larissa, Greece
                Author notes
                [* ]Corresponding author. edar@ 123456med.uth.gr
                Article
                S2214-7500(20)30432-7
                10.1016/j.toxrep.2020.11.001
                7677650
                33251119
                01fb43e4-1d2b-4840-9fd9-b4ffeef77be6
                © 2020 Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 22 July 2020
                : 30 October 2020
                : 2 November 2020
                Categories
                microRNAs: Potential biomarkers of toxicity

                glioma,glioblastoma multiforme,mirna-21,microrna,oncomir
                glioma, glioblastoma multiforme, mirna-21, microrna, oncomir

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